Sara Karlovitch, Editorial Intern

Journal of Experimental and Clinical Cancer Research has found that

a cardiotonic, known as proscillaridin A, primarily used to treat heart failure or cardiac arrhythmia is showing promise in treating patients with leukemia.

In the study, investigators observed proscillaridin A’s anticancer and epigenetic properties in juvenile leukemia wherein patients expressed the MYC gene, which, when subjected to mutations or overexpression, induces uncontrolled cell proliferation. Investigators found that the molecule attacks leukemia stem cells.

There are currently no effective, approved treatments to target the MYC gene alteration in leukemias. In order to evaluate the accuracy and efficacy of this technique, investigators utilize many techniques including those in molecular biology, next-generation sequencing, and pharmacology. As a result, the investigators observed that the molecule preferentially attacks leukemic stem cells, which drive the spread of the disease.

Using proscillaridin A to treat leukemia is a major advancement in drug repositioning, or using drugs designed for certain therapeutic indications for other disease. According to the study authors, proscillaridin A drugs have passed critical toxicology, safety, and pharmacokinetics testing and can be fast tracked for use in clinical trials.

“Each cancer is unique, and to increase the chance of survival, precision medicine is a promising way forward by developing patient- specific therapeutic strategies,” Noël J.M. Raynal, researcher at CHU Sainte-Justine and professor at Université de Montréal. "It is therefore essential to analyze the different characteristics of each cancer in genomic, epigenetic and proteomic terms in order to identify optimal therapies. Research on drug repositioning opens a new path toward innovative therapeutic options in the treatment of cancer."

While survival rates for pediatric leukemia have been improving, two-thirds of patients have long-term adverse effects from treatments that are high in toxicity, including neurological and metabolic disorders, and in some cases, secondary cancer. The repurposing of proscilaridin A to treat pediatric leukemia is step forward in making treatment less toxic and improving patient quality of life.

“In the medium term, we home to complete the preclinical characterization of this drug to eventually initiate clinical trials,” said Elodie M. Da Costa, the first author of the study. “Our ultimate goal is to identify more specific and less toxic therapeutic strategies for children with leukemia characterized by the MYC gene in order to improve survival rates and quality of life.”

Heart failure drug proscillaridin A targets MYC overexpressing leukemia through global loss of lysine acetylation. BMC website. Published June 13, 2019.

https://jeccr.biomedcentral.com/articles/10.1186/s13046-019-1242-8

Articles

A repurposed drug, known as proscillaridin A, has been found to show potential in fighting the MYC gene mutation in patients with leukemia. 

A New Purpose: Heart Failure Drug Shows Promise in Treating Leukemia

The sleep/wake patterns of “night owls” can be easily adjusted at home, leading to better eating habits and a decrease in stress and depression, according to a new study.

Over a 3-week period, investigators from the University of Birmingham and Monash University were able to shift “night owl&#39;s” circadian rhythm without pharmacological interventions. According to the study published in

, participants showed increased reaction time and strength in the morning, while feelings of stress and depression were decreased. Participants also saw their peak production time move from the evening to the afternoon and ate breakfast more often.

The study composed of 22 healthy individuals who had an average bed time of 2:30am and wake time of 10:15am. For 3 weeks, participants went to sleep and woke up approximately 2-3 hours earlier than usual, maximized outdoor light in the morning and limited light exposure in the evenings, and kept consistent meal times by eating dinner no later than 7pm. Participants kept the same wake/sleep time on work days and free days.

“Establishing simple routines could help ‘night owls’ adjust their body clocks and improve their overall physical and mental health. Insufficient levels of sleep and circadian misalignment can disrupt many bodily processes putting us at increased risk of cardiovascular disease, cancer and diabetes,” said Debra Skene, professor at the University of Surrey.

Due to “night owls” usual wake and sleep patterns, their place in society is compromised. They must go to school or work at time that is outside their preferred patterns. Addressing these differences can make our society more productive and can be applied to certain industries such as sports, according to the study.

“By acknowledging these differences and providing tools to improve outcomes, we can go a long way in a society that is under constant pressure to achieve optimal productivity and performance” said Elise Facer-Childs, MD, the lead researcher on the study.

Resetting the late timing of ‘night owls’ has a positive impact on mental health and performance. Elsevier website. Published June 10, 2019.

https://www.sciencedirect.com/science/article/abs/pii/S1389945719301388?via%3Dihub

Study shows itâ€™s possible to shift a â€œnight owlâ€™sâ€ circadian rhythm and may improve overall physical and mental health. 

Shifting the Circadian Rhythm of 'Night Owls' May Improve Mental Health

There is a significant correlation between body mass index (BMI) and psoriatic arthritis (PsA) severity according to a new study presented at the European Congress of Rheumatology.

Caused by joint inflammation, psoriatic arthritis affects the skin and joints and often leads to pain and disability. Although psoriatic arthritis has been associated with enhanced prevalence of obesity, few studies have studied the correlation between BMI and disease severity. Investigators at the European League Against Rheumatism found a independent correlation between BMI and the severity of a disease activity, patient-percieved disease impact, and disability in patients with psoriatic arthritis.

The PsABio study, an ongoing prospective observational study evaluating patients with PsA receiving ustekinumab or tumor necrosis factor inhibitors, was composed of 917 individuals across 8 European countries. Data were collected on the disease severity and patient impact and analyzed with regression models. Investigators adjusted for several factors such as: age, sex, smoking, body surface area, disease duration, biological treatment, and c-reactive protein.

In patients with PsA classified as obese or non-obese, disease activity measure cDAPSA (range 0-154) was 33.4 vs. 27.7, patient-perceived disease impact measure PsAID-12 (range 0-10) was 6.3 vs. 5.3, and disability measure HAQ-DI* (range 0-3) was 1.36 vs. 1.03 respectively

The study is part of a larger framework which evaluates how fat tissue acts as an active organ in inflammatory and metabolic disorders. Two studies presented at EULAR 2019 found that fat tissue can be used to predict the likelihood of the development of rheumatoid arthritis in subjects who are overweight, and evaluated obesity in patients with juvenile idiopathic arthritis.

“With fixed- dose drug regimens, as with self- injected biologics, obesity can reduce efficacy for pharmacokinetic reasons,” said John D. Isaacs, chairperson of the Abstract Selection Committee of EULAR. “These factors, alongside the global epidemic of overweight and obesity, makes research in this area of great relevance and interest.”

1. Being overweight linked to significantly higher disease severity in psoriatic arthritis. European Leauge Against Rheumatism, Madrid, Spain 12-15 June, 2019

https://www.eular.org/sysModules/obxContent/files/www.eular.2015/1_42291DEB-50E5-49AE-5726D0FAAA83A7D4/14_abstract_op0007_op0259_op0259_obesity_in_psoriatic_arthritis_final.pdf

The study is latest in linking fat tissue to inflammatory and metabolic disorder severity.  

Correlation Between BMI and Psoriatic Arthritis Severity Found

The varicella vaccine may reduce the risk of pediatric shingles, according to a new study by Kaiser Permanenete.

Incidents of shingles, also known as herpes zoster, were 78% lower in vaccinated children than unvaccinated children, according to research published in

Over the 12-year study period, the rate of pediatric herpes zoster fell by 72% overall as the number of children with the varicella vaccine rose.

“We saw the highest rate of HZ in the early years of the study when there was a higher proportion of children, particularly older children, who had not received the varicella vaccine,” said Sheila Weinmann, PhD, lead investigator.

The study analyzed data from over 6.3 million children between 2003 and 2014, and found that roughly 50% were vaccinated for some or all of the study period.  The number of cases of shingles among children who were not vaccinated climbed between 2003 and 2007, however, declined rapidly through the reminder of the study period. The study contributes this to two factors, increasing vaccination rates overall and the introduction of the 2-dose varicella vaccine.

“Our findings demonstrate that the vaccine does reduce the likelihood of shingles in kids, highlighting the dual benefits of the chickenpox vaccine” Weinmann said.

Shingles is caused by the varicella-zoster virus, which also causes chickenpox. Pediatric shingles is rare, despite the estimated 1 million cases of shingles every year, according to the CDC. Children also typically experience milder symptoms than adults do.

Children who received the 2- dose vaccine had a significantly lower rate of pediatric shingles than those who had the 1- dose vaccine.

1. Chickenpox vaccination lowers risk of pediatric shingles [press relesae]. AAP News & Journals website.

https://pediatrics.aappublications.org/content/early/2019/06/06/peds.2018-2917?sso=1&sso_redirect_count=1&nfstatus=401&nftoken=00000000-0000-0000-0000-000000000000&nfstatusdescription=ERROR%3a+No+local+token

. Published June 2019. Accessed June 10, 2019.

A new study finds duel benefit of the varicella vaccine. 

The Chickenpox Vaccine Reduces the Risk of Pediatric Shingles, Study Finds

Pretreatment with off-label selective vasodilator drugs prior to the implantation of left-ventricle assist devices (LVAD) may increase the chance of right-sided heart failure, according to a study published in the American Heart Association’s journal

Approximately 10% to 40% of patients who undergo a LVAD implantation for left-sided heart failure develop right-sided heart failure. In order to avoid this serious complication physicians may prescribe phosphodiesterase- 5 inhibitors (PDE5i). Several small-scale studies showed PDE5i drugs, which dilate the pulmonary artery, to have possible benefits. However, this off-label approach was never affirmed.

“We found no benefit of this therapy in patients receiving LVAD deceives, including patients with pulmonary vascular disease or right ventricular dysfunction&#151;the very patients who might be expected to benefit the most,” the senior investigator and cardiologist at Tufts Medical Center Michael Kiernan, MD, MS, said in the press release.

In the largest study to date, investigators analyzed approximately 11,544 individuals who received a LVAD in the United States between 2012 to 2017 and found that 24% of those studied experienced right-sided heart failure.

Investigators also found no benefit of pretreatment with PDE5i drugs for patients receiving left-ventricular assist devices. In the group that received the pre-treatment, 29% developed right-sided heart failure. Those who received the PDE5i drugs also experienced bleeding within a week of implantation at a rate of 46% higher than those who did not receive the drugs.

“Our findings should give pause to clinicians considering this therapy, and we caution against routine use of these therapies prior to LVAD surgery,” Kiernan said.

Preventive drug therapy may increase right-sided heart failure risk in patients who receive heart devices [press release]. American Heart Association pressroom. Published June 11, 2019.

https://newsroom.heart.org/news/preventive-drug-therapy-may-increase-right-sided-heart-failure-risk-in-patients-who-receive-heart-devices?preview=d409